The objective of this proposal is to evaluate the effect of chronic lead exposure (water-borne divalent lead) on sodium, potassium ATP-ase (NaK- ATP-ase) activity and membrane lipids in the gill of the fathead minnow Pimephales promelas. The working hypothesis is that low concentrations of soluble lead (added to aquarium water will profoundly influence gill cation transport mechanisms and eicosanoid metabolism. This hypothesis will be tested in aquarium experiments wherein adult fathead minnows will be exposed to selected concentrations of lead (2-10 ppb, as lead nitrate) for up to 3 months. Long term objectives of the Principal Investigator are to characterize this specialized ion transport epithelium in terms of similarities and differences with mammalian systems. The information thus obtained may shed light on the mechanism for chronic lead nephropathy in humans, a disease with unknown etiology. Initial efforts will focus on aquarium studies, including dose-ranging to assess the effects of lead on overall health status as well as the concentration-dependence of alterations of NaK-ATP-ase. Subsequently, the Principal Investigator will carry out time-course studies of effects of lead on gill ATP-ases and oxygen-consumption (basal and ouabain- inhibitable) to determine whether the sodium pump of gill epithelium is more susceptible to inhibition by lead relative to other gill ATP-ases. The ability of chronic lead exposure to cause lipid peroxidation injury to gill membranes will also be explored, using various indices of oxidative damage, including isoprostane production. In the final stage of the project, the effects of lead on ouabain-inhibitable oxygen consumption, lipid peroxidation and eicosanoid metabolism (cytochrome P450 pathway) in gill epithelium will be compared with those obtained in ex vivo studies with isolated renal proximal tubules from rats chronically administered lead in drinking water.